Targeting the delivery of toxins to malignant cells by complexing the toxin to monoclonal antibodies which recognize the cancer cells is becoming an effective approach to cancer therapy. The toxin-monoclonal antibody conjugates preferentially bind to and selectively kill the cancer cells [D.A. Vallera et al., Science 222: 512 (1983); E.S. Vietetta et al., Science 238; 1098 (1987)].
As a group, the trichothecenes appear to be promising toxins for the production of immunotoxins. The molecules are relatively small in size, and the class includes members with a wide range of toxic properties. Trichothecenes are potent inhibitors of protein synthesis [C.J. Carter and M. Cannon, Biochem. J. 166: 399-409 (1977); see also: Protection Against Trichothecene Mycotoxins, Natural Academy Press, Washington, DC pp. 129-138 (1983)]. This diversity provides the potential to design anticancer agents to meet specific requirements. There is a medically important need for a variety of trichothecenes.
Trichodiene was isolated from Trichothecium roseum [S. Nozoe and Y. Machida, Tetrahedron 28: 5105-5111 (1972)]and is the first intermediate in the trichothecene biosynthetic pathway. Dideacetylcalonectrin and deacetylcalonectrin are rare trichothecenes; these materials have heretofore been available only from complex synthetic methods or as minor components in fermentation broths [R. Greenhalgh et al., J. Agric. Food Chem. 34: 98-102 1986)]. It has not been previously economically feasible to produce these compounds in large quantity.